Abstract Understanding whether and how robust clinical evidence is integrated into practice is critical from the perspectives of: a) improving patient safety and health outcomes; b) designing programs and policies to accelerate the use of high value, effective treatments and abandon less effective and harmful treatments; c) containing health care costs by allocating limited health care budgets to their most effective use. In most circumstances, physicians and health care delivery organizations (HCDOs) are the key agents in determining whether a patient receives a given medical treatment. However, physician and HCDO integration of clinical evidence into practice is not well studied or understood. Our primary focus is to understand how physician networks, HCDOs and physician market environment influence the uptake of clinical evidence into clinical practice. In general, the term ?uptake of evidence?, could mean both the adoption of new treatments and de-adoption of established treatments based on new evidence related to effectiveness and/or safety. In this proposal, we will focus on the latter. We have the following aims: Aim 1: To describe variation in the uptake of clinical evidence across HCDOs, and physicians. Aim 2: To investigate how characteristics of the physician (i.e. age, gender, years since medical school or residency, patient-mix), HCDO (i.e. practice size, specialty mix, ownership, level of integration) and physician market environment (competition, malpractice environment) influence uptake of clinical evidence. Aim 3: To assess the role of physician networks (i.e. through HCDO affiliation, training in the same institution) on physicians' decision to integrate the new clinical evidence into practice. We will focus on different case studies concerning both cardiovascular (CV) and non-CV treatments with implications for CV outcomes and safety. Our study sample will include the Medicare Fee-For Service (FFS) population (from CMS) as well as the commercially insured and Medicare Advantage (MA) populations (Optum Labs).